Protein Digestion Products Research Articles

REACTIVITY OF THE SKIN OF THE NEWBORN INFANT

The skin of the full term newborn infant reacts to various dilutions of histamine phosphate with erythema but no wheal formation, as contrasted to the skin of older children where, with the same technic (scratch), whealing was frequent. The skin of the full term newborn infant is capable of fixing reagin locally. Similar fixation of antibody (and skin reactions with tendency to smaller wheals) was shown in prematurely born infants of varying ages and weight. The skin sites passively sensitized with serum containing reagin to egg showed erythema and whealing following the feeding of whole raw egg to both newborn infants and older children. This suggests that proteins or products of protein digestion, of sufficient complexity to be antigenic, are absorbed from the gastrointestinal tract of both newborn infants and older children. The above experiments support the view that the skin of the newborn infant is capable of demonstrating an antigen antibody reaction and that such reaction may be in the nature of erythema or whealing.

EFFECTS OF PROTEINURIA ON THE KIDNEY

Repeated intraperitoneal injections twice daily of various proteins into young rats were regularly accompanied by an increase in the protein content of the urine, significant renal enlargement, and often some degree of renal pallor. The most marked changes were induced by gelatin, followed in order by human albumin and bovine globulin. Rat serum produced similar but less conclusive changes. Similar changes were not produced by equivalent amounts of urea or casein hydrolysate. In sections from the kidneys of animals receiving gelatin, the cells of the convoluted tubules appeared enlarged, and they contained clear "spaces" throughout the cytoplasm. The tubular cells of the animals receiving the other solutions were not obviously altered in size or shape, and the cytoplasmic changes were slight or absent. There was little evidence of increased multiplication of cells or of tubular dilatation in the kidneys of any of the groups. Changes in concentrations of plasma proteins and hemoglobin, and the results of preliminary studies of the injected proteins in urine and renal tissue following the injections, are described and their possible significance discussed. It appears that the renal enlargement, as well as the increase in proteinuria and the tubular alterations which followed the protein injections, might have been caused in part by effects on the kidney of protein molecules per se, perhaps most likely by the effects on the tubular cells of an increased amount of protein filtered through the glomerular membranes, rather than entirely by effects of products of protein digestion and metabolism reaching the kidney through the blood stream. In the majority of animals there was no evidence from the morphological or functional studies, that the prolonged and continuous proteinuria induced by the protein injections resulted in renal damage, unless the renal enlargement, and the cytoplasmic changes which occurred regularly with gelatin, are considered evidence of damage. Renal enlargement and proteinuria promptly regressed after injections were discontinued. Lesions characterized by severe degrees of tubular damage, possibly as a result of tubular plugging, were observed in some of the animals of one group receiving gelatin solution of the usual concentration, and dilatation of renal tubules and glomerular capsules was present in some other gelatin-treated animals autopsied after relatively brief injection periods. A description is also presented of lesions of remarkable character which developed in the kidneys of all the animals of one small group receiving homologous serum obtained from severely anoxic donors. The possible relationship between the renal changes in the protein-injected animals and certain alterations of the kidneys observed in diseases characterized by large amounts of protein in the urine, is considered.

HEMOGLOBIN PRODUCTION IN ANEMIA AS INFLUENCED BY THE BILE FISTULA

The presence of a renal bile fistula with escape of all bile into the urinary tract seriously impairs the capacity of an anemic dog to form new hemoglobin on standard diets. These bile fistula dogs will produce about one-half as much hemoglobin in anemia on standard diets as during earlier control periods without a bile fistula. Iron given by mouth to an anemic bile fistula dog will effect the production of about one-half the amount of new hemoglobin as in control periods. Iron given by vein to an anemic bile fistula dog will approximate the theoretical 100 per cent return of new hemoglobin. Obviously absorption is a very important factor in the utilization of iron by these dogs. The reaction to liver feeding is much like the reaction to iron feeding but we have no proof of inadequate protein digestion and absorption in these bile fistula dogs. In fact the uniform body weight and normal clinical state over periods of years speak for adequate absorption of protein digestion products. Evidence cited above supports our belief that inadequate hemoglobin production (protein formation) noted in these bile fistula dogs may be related to a disturbed liver function.

EFFECT OF PARENTERALLY ADMINISTERED PEPTONE

The possibility of supplying the nitrogen requirements of the body parenterally led us to investigate the effect of protein split products given by this route. For many years reports have appeared in the literature on various phases of the phenomenon which has been designated peptone shock. These have included elaborate chemical studies and physiologic observations made after the parenteral and oral administration of certain protein split products. This work has all been carried out with crude products of protein digestion. In consequence the results obtained have been variable and often contradictory. REVIEW OF THE LITERATURE In 1913 Henriques and Andersen1described experiments in which they maintained goats in positive nitrogen balance by means of intravenous injections. The authors achieved this by administering a solution containing completely digested (trypsin-erepsin) meat, dextrose, sodium acetate, sodium chloride, potassium chloride, calcium chloride and magnesium chloride by continuous intravenous drip. They concluded that protein

THE EFFECT OF PROTEOLYTIC DIGESTION PRODUCTS ON MULTIPLICATION AND MORPHOLOGICAL APPEARANCE OF MONOCYTES

It has been found that the enzymatic digestion products of proteins cause a rapid proliferation of blood monocytes in vitro. Digestion mixtures having anywhere from 12 to 68 per cent of their nitrogen in the amino form possess this property. For continued proliferation, heparin plasma or serum must be repeatedly supplied with the digests. Without them, multiplication continues for only a few days, the coagulum in which the cells are embedded liquefies around the central fragment, and the cells disintegrate. The enzymatic digests exert a marked effect on the morphological appearance of the cells and finally cause them to agglutinate. The extent of this effect is determined by the degree of hydrolysis of the digest, its concentration, and the length of time the cells are cultivated in it. The morphological appearance of the cells is also somewhat influenced by the nature of the plasma or serum used with the digest. Digests having very little free amino nitrogen produce short, round, granular cells. Those more highly hydrolyzed produce large, long, slender forms. An increase in the concentration of the digest in the medium causes a shortening and broadening of the cell and an increase in its granulations. Therefore, even a highly hydrolyzed digest may, if concentrated, give cells resembling those in a lower concentration of a less hydrolyzed one. The digests have a cumulative effect on the cells, as the time of cultivation is extended. Therefore, cultivation for a long period in a dilute solution may give the same effect as a shorter time in a higher concentration. A different effect is obtained if plasma is used with the digest than if serum is used, even when the plasma and serum are taken from the same animal. The monocytes cultivated in serum and digest are generally shorter, broader, and more granular than those cultivated in heparin plasma and digest. They also contain more fat and have a greater tendency to digest the clot. Agglutination of the cells takes place more readily in highly hydrolyzed products than in those slightly hydrolyzed. It is hastened by increase in concentration of the digest in the medium. It occurs more readily at the periphery of the culture and sooner in serum and digest than in heparin plasma and digest. Completely hydrolyzed proteins and mixtures of pure amino acids do not produce effects at all comparable to those of the enzymatic digests either in their effect on the rate of cell proliferation or their action on the morphology of the cell. Arsenic pentoxide in dilutions from 1:20,000 to 1:80,000 is the only other agent known to bring about agglutinations of the monocytes when cultivated in vitro. The early changes in the morphological appearance of the cell that are produced by these digests are reversible. When the digests are removed from the medium and the cells cultivated in plasma and Tyrode solution, they very gradually revert to their original form.

Studies in passive transfer. 4. Rectal absorption of the antigen (egg white)

N VIEW of the interest in allergic as well as physiologic phenomena, the question of colonic absorption is important. This report presents data obtained in a study of that question. The products of protein digestion in vitro differ from the original protein by being slightly diffusible. For some time it was assumed that only diffusible protein was absorbed and hence that peptonization was essential. Schloss and Worthen,l however, demonstrated by precipitin and anaphylactic tests, that foreign protein might be absorbed. in an undigested or partially digested state. This has been more recently confirmed by Walzer2 by application of the local passive transfer phenomenon described by Prausnitz and Ktistner.3 Walzer showed that, in adults, oral administration of the antigen gave results quite comparable with those obtained by injection in the local sensitized skin areas. In a previous study4 me have reported similar results in new’born infants. There has remained, however, the question as to the site of this absorption in the intestinal tract. The opinion in many textbooks is that. absorption takes place above the cecum and that only water a.nd crystalloids are absorbed from the large bowel. The contrary evidence of Voit? has apparently been overlooked. Following rectal a.dministration of egg white and salt solution, they found an increase in urinary nitrogen. Since it was, known that practically no peptonization took place in the colon and since the effect of enzymes could be ruled out, absorption probably accounted for their findings. Egg white represents a nonassimilable type of protein in colztrast with its acid albumin fraction. Introduced in the blood stream the former substance is excreted by the kidney. Schloss and Worthenl demonstrated the presenee of egg white in the urine following oral administration. They emphasized the greater absorption from upset or abnormal intestinal t.racts. Colonic absorption is suggested from their findings since with increased peristalsis the chance of absorption from the upper intestinal tract is 1es.s. Yet it has been shown by previous passive transfer studies4 that the majority of healthy yoang infants will absorb egg white antigen after oral administration. The f olloming experiments were designed to see if application of local passive trans-

The Titration Curve of Gastric Mucin

Fogelson has prepared a “gastric mucin” from the gastric mucosa of hogs which has a relatively high combining power for free hydrochloric acid and which has proved to be effective in relieving the symptoms of peptic ulcer when administered in adequate doses. Kim and Ivy have found that the administration of “gastric mucin” prevents the development of duodenal ulcers in biliary fistula dogs. Since Fogelson did not claim that his “gastric mucin” was a pure product, since with his method of preparation, it is very likely that peptone and other products of incomplete protein digestion are present which may account for some of the acid-combining properties of his product, and since we were interested in the mechanism by which “gastric mucin” relieved the symptoms of ulcer and apparently promoted healing, we decided to wash Fogelson's mucin more thoroughly with 60% ethyl alcohol and compare the titration curves of the washed and unwashed “mucins”. A weighed quantity (50 gm.) of Fogelson's mucin was extracted 4 times with 500 cc. of 60% ethyl alcohol, in which peptone is soluble and mucin is insoluble. It was found that about 60% of Fogel-son's mucin is soluble in 60% ethyl alcohol and 40% is insoluble. Figure I shows the titration curves of 1 gm. each of Fogelson's gastric mucin (A), the peptone or 60% alcohol soluble fraction (B), the mucin or 60% alcohol insoluble fraction (C), Armour's meat peptone (D), and gelatin (E), in solution in 50 cc. of distilled water. Sufficient sodium hydroxide was added to each solution to give it a pH of 8.0 before the titration with N/10 HCl was started. This was done because it was found that the pH of different batches of Fogelson's mucin obtained from the manufacturing firm (Armour and Co.) varied from pH 7.5 to 8.0.

Allen's commercial organic analysis. Edited by C. Ainsworth Mitchell, M.A., D.Sc., F.T.C., and several contributors. Vol. VIII.‐Glucosides, Non‐Glucosidal Bitter Principles, Enzymes, Putrefaction Bases, Animal Bases, Animal Acids, the Cyanogen Compounds, the Proteins, the Digestion Products of Proteins. 5th edition, revised and partly rewritten. Pp. x+761. London: J. & A. Churchill, 1930. 30s

Allen's commercial organic analysis. Edited by C. Ainsworth Mitchell, M.A., D.Sc., F.T.C., and several contributors. Vol. VIII.‐Glucosides, Non‐Glucosidal Bitter Principles, Enzymes, Putrefaction Bases, Animal Bases, Animal Acids, the Cyanogen Compounds, the Proteins, the Digestion Products of Proteins. 5th edition, revised and partly rewritten. Pp. x+761. London: J. & A. Churchill, 1930. 30s

Preliminary Note on Inhibition of Bacterial Growth by Amino-acids

While amino-acids in appropriate concentrations have long been known as valuable aids to bacterial growth, it does not appear to have been recognised that in relatively low concentrations they are often inhibitory.Inhibition has been shown to occur with 10 out of 11 single amino-acids tested and with certain mixtures rich in amino-acids. The inhibitory concetration varies from 11 to 130 millimols per litre, or from 0·2 to 2%(wt./vol. ). It is of some intrest that the amino-acids inhibitory in the lowest concentration were the cyclic compounds—histidine, tyrosine, tryphane, phenylalamine. Of the chain compounds tested cystine was the most inhibitory.Several organisus belonging to various groups of bacteria are susceptible of inhibition by amino-acids; certain intestinal organisms are not susceptible. The effect cannot be attributed to the physical effects of high concentration.There is an apparent divergence between our results and those of workers who have recommended tryptic digests for stimulating the growth of some of the bacteria here shown to be readily inhibited by amino-acids. A suggested explanation of this divergence is that it is the products of partial protein digestion, the polypetides, which are mainly responsible for the effect of stimulating growth, not the amino-acids. A “polypeptide medium” might prove particularly valuable for bacterial growth.A metabolism experiment with glycine in high but sub-inhibitory concentration showed that the amino-acid is broken down by Staphylococcus aureus, at this concentration.

The bacteriology of the blood of dogs with Eck fistula

There is an impression, supported by considerable evidence, that organisms from the bowel often enter the portal stream and in the liver are effectively disposed of. In order to test this point it was thought that Eck fistula dogs might furnish proper conditions; at least, it would be of interest to note whether or not bacteria appeared in the general circulation or possibly caused occasional infections in the lungs or elsewhere in such animals. An Eck fistula is an artificial communication between the portal vein and the vena cava with the portal vein ligated above the anastomosis just at the hilus of the liver. This operation destroys the portal circulation so far as the liver is concerned, in that now the flow of blood from the abdominal viscera (except the kidneys and the suprarenal glands) is returned to the general circulation without passing through the capillaries of the liver; in other words, the liver is shunted out of the portal circulation and receives its sole blood supply by way of the hepatic artery, which carries about one-fifth of the quantity of blood that is carried by the portal vein. The anatomic situation of the liver naturally suggested to investigators a protective function. Under normal condition all the products of intestinal digestion and other absorbable substances (except the greater part of the fats) must first pass through the liver capillaries before reaching the tissues in general, while under the conditions imposed by an Eck fistula they reach the tissues first. It has been amply proved that the liver exercises a protective function against certain poisons absorbed from the alimentary tract, especially against certain of the products of protein digestion, such as ammonia. In fact, dogs with Eck fistulas will not tolerate a heavy meat diet. To prove whether or not bacteria actually pass the bowel wall into the circulation and, if so, what influence the liver has on them, we instituted the following experiments on dogs with Eck fistula.

IMMUNITY AND THE POWER OF DIGESTION

Previous articleNext article FreeJournal ArticlesIMMUNITY AND THE POWER OF DIGESTIONVERA DANCHAKOFFVERA DANCHAKOFFCOLUMBIA UNIVERSITY Search for more articles by this author COLUMBIA UNIVERSITYPDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by The Biological Bulletin Volume 38, Number 4April 1920 Published in association with the Marine Biological Laboratory Article DOIhttps://doi.org/10.2307/1536325 Views: 27Total views on this site © 1920 Marine Biological LaboratoryPDF download Crossref reports no articles citing this article.

The Antigenic Properties of Proteoses

Of fundamental importance in immunity is the question whether only proteins are antigenic. Wells1 says, yet, it has not been finally established that any colloids other than proteins can act as antigens. Assuming then, that only proteins possess antigenic properties, it becomes of interest to inquire what there is in the nature or constitution of proteins to which this is due. Two characteristics of proteins have received the greatest attention in this connection; their colloid nature and their huge molecular weight. Attempts to explain the antigenic properties of proteins on the basis of their colloid nature have been largely speculative and consist of the application of the principles of colloid chemistry to theories of immune reactions. The efforts to determine the influence of the size of the molecule on the antigenic properties of proteins have led to numerous attempts to produce antibodies for the products of protein hydrolysis and digestion. Our understanding of the chemistry of immune reactions is limited by our knowledge of the chemistry of proteins. Each new insight into the nature and constitution of proteins is followed by a readjustment of our theories of immuno-chemistry. Underbill and Hendrix2 place the discovery of the phenomenon of anaphylaxis among the more important recent advances in the physiology of proteins. It has also furnished considerable impetus to the study of protein chemistry. For a satisfactory explanation of the anaphylaxis reaction, jt became necessary to determine by what changes proteins were rendered toxic, since it was well known that native proteins were of themselves nontoxic. This led to the theories of Vaughan, Friedmann and Friedberger that anaphylaxis is due to parenteral digestion of proteins, and that the symptoms are due to intoxication with the resulting products. To obtain evidence in support of these theories the products of protein

A STUDY OF AMINO NITROGEN AND GLUCOSE IN LYMPH AND BLOOD BEFORE AND AFTER THE INJECTION OF NUTRIENT SOLUTIONS IN THE INTESTINE

The question of the absorption of protein by way of the lymph has not been considered since the true significance of protein digestion has been known. The earlier investigators were limited to the determination of total nitrogen as a means of following the products of protein digestion through the body. Newer methods make it possible and desirable to follow resorption of the products of protein digestion by the determination of amino nitrogen in the tissues and fluids of the body.

A NEW AND EFFICIENT METHOD OF CULTIVATING BACILLUS LEPRÆ FROM THE TISSUES

In a previous communication¹one of us (Duval) stated that the initial multiplication<i>in vitro</i>of the bacillus found in leprosy lesions is attended with considerable difficulty unless bits of the infected tissue are transferred to the culture-medium and special methods employed for the breaking down of the tissue protein. In other words, the removed tissue particles must be hydrolyzed before the contained acid-fast bacilli will multiply. The difficulty in continuing the multiplication in subcultures occurs as soon as the digested tissue material has been exhausted. Therefore it is absolutely essential to substitute at some period in the process a medium which contains split products of protein digestion, such as the amino-acids, until the culture has accustomed itself to more or less saprophytic conditions. Early in the work on the cultivation of acid-fast bacilli from leprous lesions it was noted that, in the removed tissue bits which had become